Acellular red blood cell substitute

Abstract

An acellular red blood cell substitute which comprises an essentially tetramer-free, substantially stroma-free, cross-linked, polymerized, pyridoxylated hemoglobin and a nontoxic, pharmaceutically acceptable carrier, its use and a process for preparing said acellular red blood cell substitute.

Description

[0001]This is a continuation of application Ser. No. 09 / 995,203, filed Nov. 27, 2001, now U.S. Pat. No. 6,552,173, which is a continuation of application Ser. No. 09 / 638,471, filed Aug. 14, 2000, now U.S. Pat. No. 6,323,320, which is a continuation of application Ser. No. 08 / 484,942, filed Jun. 7, 1995, now U.S. Pat. No. 5,747,649, which is a continuation of application Ser. No. 08 / 031,563, filed Mar. 15, 1993, now U.S. Pat. No. 6,133,425, which is a continuation of application Ser. No. 07 / 616,727, filed Nov. 21, 1990, now U.S. Pat. No. 5,194,590, which is a continuation of application Ser. No. 07 / 315,130, filed Feb. 23, 1989, now abandoned, which is a continuation of application Ser. No. 06 / 876,689, filed Jun. 20, 1986, now U.S. Pat. No. 4,826,811.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]This invention relates to an acellular red blood cell substitute comprising an essentially tetramer-free, cross-linked, polymerized, pyridoxylated hemoglobin solution which i...

AI Technical Summary

Benefits of technology

[0011]A still further object is to provide a temporary oxygen carrier which can be rendered substantially free of microbial and viral antigens and pathogens.

Problems solved by technology

For years investigators have reported that hemoglobin solutions prepared by various techniques, while capable of carrying sufficient quantities of oxygen to support life, have undesirable side effects.

The most troubling side effect is a decrease in kidney performance.

While contaminants such as these can indeed produce renal alterations, hemoglobin solutions essentially free of the above contaminants still produce substantial renal dysfunction.

Although this dysfunction is temporary and reversible, it can be very alarming in a clinical situation such as hemorrhagic shock, as the kidney is already at risk in this low blood flow state.

Other undesirable side effects of the infusion of tetrameric hemoglobin are renal toxicity, vasoconstriction, hemoglobinurea, depression of heart rate, elevation of mean arterial blood pressure and extra-vasation of infusate especially into the peritoneal cavity.

In practice, no known hemoglobin-derived blood substitute has been successful in totally avoiding toxicity problems These products prepared according to the state of the art have been found to contain varying amounts of hemoglobin tetramer.

For example, the process of preparation according to U.S. Pat. Nos. 4,001,200; 4,001,401 and 4,053,590 does not provide a therapeutically useful product.

First, like other proceses, there is an undesirable, high amount of unpolymerized hemoglobin tetramer in the final product.

Secondly, too many contaminants such as toxic residual toluene may remain in the solution since they may not be completely removed during preparation.

Thirdly, the product, described as having a P50 of 100-120 mm Hg, would be nonfunctional physiologically in that the hemoglobin solution would not pick up oxygen in the lungs.

Lastly, increased proportions of higher molecular weight polymers yield a product of high gelation lability such that subsequent steps of filtration and purification are difficult or impossible to accomplish except in unacceptably dilute solutions.

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